The cell membrane is well recognized as a primary target for the pathological action of both disease processes and environmental pollutants and the overall objective of this project is to evaluate the role of selective membrane permeability and transport in the overall function of epithelial cell tissues. Combined physiological and morphological techniques, such as autoradiopraphy and isolation of cell membranes, are being employed to investigate basic mechanisms of epithelial cell transport using several lower vertebrate models: A. Regarding the role of individual transport steps for PAH-like organic acids, we have used purified membrane vesicles from flounder kidney cells to demonstrate the first unequivocal example of a carrier-mediated step at the luminal or brush border membrane. Also, we have shown autoradiographically in flounder kidney that the acidic DDT metabolite, DDA, is transported by at least the peritubular membrane step. B. Regarding the role of ouabain sensitive, Na,K-ATPase powered, sodium pump in specialized salt transporting epithelia, we have used 3H-ouabain sutoradiography to localize the enormous Na,K-ATPase activity in elasmobranch rectal gland cells to the basal-lateral membrane. Furthermore, we have demonstrated with rectal gland membrane vesicles the existance of a coupled Na/Cl co-transport carrier which appears to provide the basis for uphill chloride secretion by the Na,K-ATPase maintained sodium gradient. A similar coupled Na/Cl carrier has also been identified in flounder intestine, but not kidney.